TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary.
This week’s topics include antibody persistence after COVID, community prevalence of five diseases and severe COVID, cardiac abnormalities after COVID, and genetic variants and severe COVID.
0:46 County level prevalence of underlying medical conditions and COVID
1:48 Allow for allocation of resources
2:45 More in rural areas
3:49 Diabetes in 40%
4:06 COVID and heart conditions
5:06 In the interstitium
6:04 Will this have long term effects?
7:04 Doesn’t actively kill cells
7:22 Gene variants in young men with severe COVID
8:22 Impacted on interferon signaling
9:26 Two phases of infection
10:06 How long antibodies persist in mild COVID
11:08 Gauge half-life
12:06 Wear a mask
Elizabeth Tracey: Genetic variance among young men with severe COVID-19 disease.
Rick Lange: How long do COVID antibodies persist?
Elizabeth: What are the estimated county-level prevalences, if you will, of underlying medical conditions associated with increased risk for severe COVID-19?
Rick: And COVID-19 infections and the heart.
Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore–based medical journalist.
Rick: And I’m Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso, where I’m also the Dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, how about if we turn to the CDC to MMWR, Morbidity and Mortality Weekly Report, this study that’s taking a look at county-level prevalence of underlying medical conditions that are associated with the risk for development of severe COVID-19 illness?
They took a look at five different underlying diseases — COPD, cardiovascular disease, diabetes, chronic kidney disease, and obesity — and they also used data from a self-reported database that’s called the Behavioral Risk Factor Surveillance System, and U.S. Census population data.
They looked at these conditions among residents in over 3,100 counties in all 50 states and the District of Columbia, and they found the median prevalence of any underlying medical condition in these residents was pretty close to 50% — all right, it was 47.2% — and that’s, of course, significant.
They found that the counties with the highest prevalence were concentrated in the southeast and the Appalachian regions. That’s not surprising. We’ve talked a lot about those particular regions before. They basically say, “Hey, this is going to allow people to allocate resources in such a way that we can make sure that we’re ready for the presence of severe COVID-19 disease in these populations.”
Interestingly, these were not urban areas, largely. They were rural and ex-urban areas where the actual numbers based on the population levels were higher.
Rick: As you mentioned, about half of the individuals in these counties had one or more of those, with obesity and diabetes being the top two risk factors.
Now, what they didn’t do was they couldn’t weight it. I’m sure each of those risk factors is more likely to contribute to severe disease, meaning those are more likely to be hospitalized, on a ventilator, in the ICU, shock, or experience death. But it is disconcerting that, as widespread as the pandemic is, these risk factors are really prevalent throughout most counties in the United States and more so in rural and non-metropolitan areas, where resources are more scarce.
Elizabeth: Exactly. They also note that an analysis of all of the patient surveillance data so far on US COVID-19 patients indicates that hospitalizations are 6 times higher, ICU admissions 5 times higher, and deaths 12 times higher among patients with underlying medical conditions, including these ones that they took a look at in here.
Specifically, the states that had the highest prevalence of any condition were Alabama, Arkansas, Kentucky, Louisiana, Mississippi, Tennessee, and West Virginia. There were also some counties in Oklahoma, South Dakota, Texas, and Northern Michigan that had much more prevalent disease.
Rick: Now, again, the numbers of patients are going to be higher in the large metropolitan areas, but the prevalence is going to be higher in these areas that we mentioned. Again, oftentimes these are areas that really don’t have the resources to handle these high number of patients that are likely to have a severe manifestation of the illness.
Elizabeth: Right, and a lot of these places are places that haven’t really… Some of them have experienced a surge so far, but some of them haven’t, so I guess this is a question of preparation. I would just note — not in this study, but in another one I saw — that it was taking a look just at diabetes and suggests that 40% of patients with severe COVID-19 disease had diabetes.
Rick: The vast majority of these individuals with severe COVID disease will have one or more of the risk factors we’ve mentioned.
Let’s talk about COVID disease and heart conditions. We’ve already talked about the fact that heart disease predisposes to getting severe illness — heart disease meaning hypertension or coronary artery disease, or even heart failure. There have been some reports of active heart inflammation, what’s called myocarditis, and how prevalent is heart manifestations? What kind of heart manifestations are there?
There were actually two articles that were published in the JAMA Cardiology. One was an autopsy study and the other is an imaging study, so we’ll cover the autopsy study first. They did 39 consecutive autopsies on COVID-19 patients that really hadn’t died of heart disease, so the vast majority had died of pneumonia.
This was done in Germany over about a week and a half period. They could detect virus in almost two-thirds of the autopsy specimens. Not only did they look for virus, but they actually look at the viral load. In the patients that had virus detected, about two-thirds of them had what’s called a high viral load.
Interestingly enough, it wasn’t in the heart muscle itself. It was in the interstitium — that is the place between the heart muscles — and oftentimes in the macrophages. There wasn’t a lot of active inflammation or lymphocyte infiltration, things that indicate active myocarditis, but it was detected.
Now, the other study was an MRI study. This was conducted in 100 patients. They compared those to 50 control patients that didn’t have COVID infections and 50 patients that had risk factors like the COVID patients.
What they determined is that there were MRI abnormalities in about 70% of the COVID patients. They also found evidence of edema, or swelling, in the heart muscle as well in about three-fourths. Now, these weren’t people that had active COVID infection. These were people that were studied over about 5 weeks to as long as 12 or 13 weeks after active infection, so these are more long-lasting effects.
Elizabeth: Clearly, something that’s going to need to be followed up even longer, since it appears to be lots of us searching for our long-term sequelae of infection.
Rick: Right. Now, these are people that didn’t have heart symptoms. But the question, as you mentioned, is, “Will this have long-term deleterious effects? Will people develop heart enlargement? Will they develop a cardiomyopathy? Will they develop heart failure over the subsequent years?” That is unknown.
To dig a little bit deeper, the average age of these individuals that had the MRI study was about 49, so they’re relatively young. That means we need to follow them over subsequent decades to see whether there are long-term deleterious effects.
Elizabeth: Another study that came up — that, again, we’re not talking about today — was looking at infection of the olfactory epithelium by the coronavirus. Initially, there was a lot of discussion about the presence of a high level of ACE-2 receptors in that area.
In this particular study, they demonstrated that in fact it doesn’t infect the neurons. It affects the sustentacular cells, the cells that are there to help support it. I’m interested in the idea that the high viral load was found in the interstitium and not in the cardiomyocytes.
Rick: That really is interesting because it speaks to the fact that it doesn’t cause active death of the myocyte cells directly, but there are some indirect effects. Myocardial cells do have COVID receptors, these ACE receptors, but they’re relatively few compared to the nasal epithelium and to the lung epithelium.
Elizabeth: More coming, no doubt, for the nerds among us who are interested in this. Speaking of nerds, let’s turn to a preliminary communication that’s in the Journal of the American Medical Association. This is taking a look at the presence of severe COVID-19 disease in two pairs of brothers.
These guys are young. Their mean age was 26 years, age range from 21 to 32, no history of major chronic disease, previously healthy, became infected with COVID-19, and then ultimately required mechanical ventilation in the ICU.
One of these patients, of these four previously healthy young guys, died, and what they did was rapid clinical whole exome sequencing of their DNA and available family members. They found that there were two mutations — or variations, let’s call them — in each of the families.
One of them was a maternally-inherited four-nucleotide deletion, and the other one was a missense variant. What both of these things did was they impacted on downstream interferon signaling and a reduced production of interferon gamma.
The interesting thing about this study, of course, is that they’re drilling down into, “What could be causing more serious disease in people who were previously looked to be healthy?”
Rick: Genetic variance all honed in on the same thing, what’s called toll-like receptor 7, or TLR-7, a pathway that goes towards making gamma interferon, which is used, by the way, as one of the immune system’s responses to try to decrease viral replication. These guys didn’t have it and as a result they had severe infection, most likely as a result of the fact that they were unable to dampen down the immune response.
Now, Elizabeth, we’ve alluded to the fact there are probably two phases. There is the initial phase, where there’s viral replication and the virus’s titer’s growing larger, and we want to try to diminish that. Then there is the later phase, where that causes a severe immune response, an inflammatory response, and you want to dampen that. The initial treatment is to try to decrease viral replication — that’s where remdesivir and other antiviral agents may be beneficial — and later, with the inflammatory response, that’s where steroids become most helpful. Fortunately, this is a really pretty rare genetic abnormality, but it does give us insight into the phases of the disease.
Elizabeth: Right, and also the importance of the interferon.
Rick: Absolutely. Now, by the way, they could increase their interferon response to some infections — like Candida or yeast infections — but it didn’t do it in response to the COVID infection, so it was very limited, and again, it’s due to a specific receptor.
Elizabeth: Let’s end with your final one, which is something that’s a lot of concern to a lot of people, and that’s what happens to antibodies against COVID infection after people have had a mild infection? This is in correspondence in the New England Journal of Medicine.
Rick: The study was limited to people that had a mild infection and the question is, “Well, they must develop an antibody response that helps. How long does that antibody response last?”
They identified about 80 patients that had a mild response, and of those, about 41 had at least two or three different blood samples in which they could measure the antibody. These samples were obtained not immediately, but 30 days after the onset of symptoms, and the second one was obtained somewhere between 60 and 120 days after the onset of symptoms.
What they were able to do is, first of all, document that everybody did have an antibody response — some were more robust than others — and then they followed a decline, and that is not all, but many of the individuals had a decline in antibodies. They were able to gauge what the half-life was, when do you expect half the antibodies to be gone. In this population, it was 73 days, so people mount a very vigorous antibody response and 73 days later that antibody response has decreased by 50%.
Now, here’s what we don’t know. It doesn’t tell us that they still have had adequate antibody. We don’t know whether they can get infected again. We don’t know what’s going to happen over the next 70 or 120 days. Decay may decline even more after that, but it does indicate that there obviously is a decline in antibodies that occurs relatively soon after the infection.
Elizabeth: I, for one, am not going to gloom and doom over this because we’ve talked before, also, about the importance of the T-cell response in subsequent infection, or the potential for subsequent infection. I’m just not prepared to start wringing my hands over declining antibodies at this point.
Rick: No, and Elizabeth, I would agree with that. However, I do get concerned because people that say they’ve had an infection, that they have what’s called the so-called “immunity passport.” They don’t have to wear a mask. They don’t have to socially distance. They don’t have to wash their hands because they’ve already been infected and they’re protected.
We actually don’t have enough information to suggest that that’s true nor do we have enough information to suggest that we’ll have enough antibody response across the population to develop herd immunity. But even if we develop a vaccine, will that have long-sustaining immune responses?
As you said, antibody is not the only response, the T cells are also important. There’s a lot more information, but I want all our listeners to say that just because you have an infection doesn’t necessarily mean that you’re protected. Still do the protective measures we’ve talked about.
Elizabeth: On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.
Rick: I’m Rick Lange. Y’all listen up and make healthy choices.